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Cancers Jul 2020Cutaneous T-cell lymphomas (CTCLs) represent a large, heterogeneous group of non-Hodgkin lymphomas that primarily affect the skin. Among multiple CTCL variants, the most... (Review)
Review
Cutaneous T-cell lymphomas (CTCLs) represent a large, heterogeneous group of non-Hodgkin lymphomas that primarily affect the skin. Among multiple CTCL variants, the most prevalent types are mycosis fungoides (MF) and Sézary syndrome (SS). In the past decade, the molecular genetics of CTCL have been the target of intense study, increasing the knowledge of CTCL genomic alterations, discovering novel biomarkers, and potential targets for patient-specific therapy. However, the detailed pathogenesis of CTCL development still needs to be discovered. This review aims to summarize the novel insights into molecular heterogeneity of malignant cells using high-throughput technologies, such as RNA sequencing and single-cell RNA sequencing, which might be useful to identify tumour-specific molecular signatures and, therefore, offer guidance for therapy, diagnosis, and prognosis of CTCL.
PubMed: 32751918
DOI: 10.3390/cancers12082129 -
International Journal of Molecular... Feb 2024Mogamulizumab (MOG) is an antibody targeting the CCR4 receptor, authorized for relapsed or refractory peripheral T-cell (PTCL) and cutaneous T-cell lymphomas (CTCL). Its... (Review)
Review
Mogamulizumab (MOG) is an antibody targeting the CCR4 receptor, authorized for relapsed or refractory peripheral T-cell (PTCL) and cutaneous T-cell lymphomas (CTCL). Its adoption in guidelines and endorsement by FDA and EMA established it as a systemic treatment, especially for advanced disease stages due to its comparatively lower toxicity. Clinical trials and real-world evidence have underscored its efficacy in advanced CTCLs, including mycosis fungoides and Sézary syndrome; PTCLs; and adult T-cell leukemia/lymphoma (ATLL), showcasing positive outcomes. Notably, the drug has demonstrated significant response rates, disease stability, and extended periods of progression-free survival, suggesting its applicability in cases with multiple treatment lines. Its safety profile is generally manageable, with adverse events (AEs) primarily related to the skin, infusion-related reactions, drug eruptions, autoimmune diseases, and skin disorders. The latter seem to appear as CCR4 can promote the skin-specific homing of lymphocytes, and MOG is directed against this receptor. While combination with immunostimulatory agents like interferon alpha and interleukin 12 has shown promising results, caution is urged when combining with PD1 inhibitors due to the heightened risk of immune-mediated AEs. The introduction of MOG as a systemic treatment implies a significant advancement in managing these diseases, supported by its favorable safety profile and complementary mechanisms.
Topics: Adult; Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Leukemia-Lymphoma, Adult T-Cell; Skin Neoplasms; Antibodies, Monoclonal, Humanized
PubMed: 38396877
DOI: 10.3390/ijms25042203 -
Giornale Italiano Di Dermatologia E... Dec 2019Cutaneous T cell lymphoma (CTCL) is a non-Hodgkin's lymphoma with a heterogenous presentation and highly variable disease course. The most common subtypes of CTCL are... (Review)
Review
Cutaneous T cell lymphoma (CTCL) is a non-Hodgkin's lymphoma with a heterogenous presentation and highly variable disease course. The most common subtypes of CTCL are mycosis fungoides (MF) and Sézary Syndrome (SS). Treatment varies based on the stage of the disease with skin directed therapies typically utilized for early stage disease, and systemic therapies employed for more advanced disease. There are few highly effective treatments available, and systemic therapies have limited response rates. Histone deacetylase inhibitors have emerged as mainstream treatments for MF/SS over the past several years. Here, we discuss the mechanism of action of histone deacetylase inhibitors in relation to the pathogenesis of MF/SS, evaluate the clinical trials that led to Food and Drug Administration approval of two of the histone deacetylase inhibitors for MF/SS and describe the results for those still under investigation. Additionally, we discuss the potential for combination therapies in order to optimize outcomes of treatment with histone deacetylase inhibitors.
Topics: Animals; Histone Deacetylase Inhibitors; Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Neoplasm Staging; Sezary Syndrome; Skin Neoplasms
PubMed: 31859467
DOI: 10.23736/S0392-0488.19.06503-9 -
Acta Dermato-venereologica Mar 2022Aggressive primary cutaneous T-cell lymphomas include advanced-stage mycosis fungoides (stage ≥ IIB mycosis fungoides), Sézary syndrome, gamma/delta cutaneous...
Aggressive primary cutaneous T-cell lymphomas include advanced-stage mycosis fungoides (stage ≥ IIB mycosis fungoides), Sézary syndrome, gamma/delta cutaneous lymphoma, nasal type lymphoma, aggressive epidermotropic CD8+ T-cell lymphoma and some cutaneous lymphomas not otherwise specified. To evaluate their long-term prognosis, we conducted a retrospective cohort study of 85 patients diagnosed between 2005 and 2020 with advanced-stage mycosis fungoides (n = 48), Sézary syndrome (n = 28) or aggressive non-mycosis fungoides/Sézary syndrome subtypes (n = 9). The median survival times in these 3 groups were 118.7, 45.7 and 11.2 months, respectively, and the 5-year survival rates were 55.3%, 27.8% and 33.3%, respectively. Multivariate analyses in patients with mycosis fungoides/Sézary syndrome identified age ≥ 70 years, Eastern Cooperative Oncology Group Performance Status ≥ 2, and the high-risk group according to the Cutaneous Lymphoma International Consortium prognostic model, as adverse prognostic factors. Seven patients in this mycosis fungoides/ Sézary syndrome group were in complete long-term remission after treatment with bexarotene, including 4 patients living without any treatment for 16-101 months.
Topics: Aged; Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Prognosis; Retrospective Studies; Sezary Syndrome; Skin Neoplasms
PubMed: 35083494
DOI: 10.2340/actadv.v102.1087 -
Cancers Oct 2020Cutaneous T-cell lymphomas (CTCLs) are non-Hodgkin lymphomas that develop primarily in the skin. They account for almost 80% of primary cutaneous lymphomas.... (Review)
Review
Cutaneous T-cell lymphomas (CTCLs) are non-Hodgkin lymphomas that develop primarily in the skin. They account for almost 80% of primary cutaneous lymphomas. Epidermotropic CTCLs (mycosis fungoides (MF) and Sézary syndrome (SS)) are the most common form of CTCL. The course of the disease ranges from an indolent clinical behavior in early-stage disease to an aggressive evolution in the advanced stages. Advanced-stage disease is defined by the presence of tumors, erythroderma, or significant blood, nodal or visceral involvement. Advanced-stage disease is characterized by frequent disease relapses, refractory disease, a severely impaired quality of life and reduced overall survival. In the last twenty-five years, allogeneic hematopoietic stem cell transplantation (HSCT) has led to prolonged remissions in advanced CTCL, presumably linked to a graft-versus-lymphoma effect and is thus emerging as a potential cure of the disease. However, the high post-transplant relapse rate and severe morbidity and mortality associated with graft-versus-host disease and infections are important issues. Allogeneic HSCT is thus mostly considered in young patients with no comorbidities and an aggressive, advanced-stage CTCL. Allogeneic HSCT gives the best results in patients with a pre-transplant complete remission of the lymphoma. For this reason, one of the challenges is to define the best time to consider allogeneic HSCT in the disease course. Early identification of patients at high risk for progression is important to identify candidates who may benefit from allogeneic HSCT before their disease becomes treatment-refractory. This review describes the role of allogeneic HSCT in CTCL, summarizes the published data and future perspectives in this area.
PubMed: 33023002
DOI: 10.3390/cancers12102856 -
Actas Dermo-sifiliograficas Jan 2021Primary cutaneous T-cell lymphomas other than mycosis fungoides, Sézary syndrome, and lymphoproliferative CD30 disorders are few, accounting for less than 5% of all...
Primary cutaneous T-cell lymphomas other than mycosis fungoides, Sézary syndrome, and lymphoproliferative CD30 disorders are few, accounting for less than 5% of all cutaneous lymphomas. A cytotoxic phenotype is characteristic of these tumors, and their clinical behavior is usually aggressive. Patients often present with extracutaneous symptoms or develop them shortly after diagnosis. Management is usually multidisciplinary, and intensive systemic therapy and bone marrow transplantation should be considered. Cutaneous B-cell lymphomas account for approximately 30% of primary cutaneous lymphomas. They make up a heterogeneous group of tumors that have different clinical and pathological features. Clinical course also varies. Presenting as papules, nodules, or tumors of variable reddish-violaceous coloring, the lesions may be solitary or multiple and occasionally form clusters. There may also be generalized lesions, present at multiple sites on the trunk, head, or extremities. Three well-defined groups of primary cutaneous lymphoma have been reported: follicle center lymphoma; marginal zone lymphoma, which follows an indolent course; and a diffuse large B-cell lymphoma, leg type, which follows an aggressive course.
Topics: Humans; Lymphoma, Follicular; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms
PubMed: 33045210
DOI: 10.1016/j.ad.2020.09.005 -
Clinical Advances in Hematology &... Sep 2021
Topics: Humans; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms
PubMed: 34495021
DOI: No ID Found -
Blood Dec 2021Sézary syndrome (SS) is an aggressive leukemic form of cutaneous T-cell lymphoma with neoplastic CD4+ T cells present in skin, lymph nodes, and blood. Despite advances...
Sézary syndrome (SS) is an aggressive leukemic form of cutaneous T-cell lymphoma with neoplastic CD4+ T cells present in skin, lymph nodes, and blood. Despite advances in therapy, prognosis remains poor, with a 5-year overall survival of 30%. The immunophenotype of Sézary cells is diverse, which hampers efficient diagnosis, sensitive disease monitoring, and accurate assessment of treatment response. Comprehensive immunophenotypic profiling of Sézary cells with an in-depth analysis of maturation and functional subsets has not been performed thus far. We immunophenotypically profiled 24 patients with SS using standardized and sensitive EuroFlow-based multiparameter flow cytometry. We accurately identified and quantified Sézary cells in blood and performed an in-depth assessment of their phenotypic characteristics in comparison with their normal counterparts in the blood CD4+ T-cell compartment. We observed inter- and intrapatient heterogeneity and phenotypic changes over time. Sézary cells exhibited phenotypes corresponding with classical and nonclassical T helper subsets with different maturation phenotypes. We combined multiparameter flow cytometry analyses with fluorescence-activated cell sorting and performed RNA sequencing studies on purified subsets of malignant Sézary cells and normal CD4+ T cells of the same patients. We confirmed pure monoclonality in Sézary subsets, compared transcriptomes of phenotypically distinct Sézary subsets, and identified novel downregulated genes, most remarkably THEMIS and LAIR1, which discriminate Sézary cells from normal residual CD4+ T cells. Together, these findings further unravel the heterogeneity of Sézary cell subpopulations within and between patients. These new data will support improved blood staging and more accurate disease monitoring.
Topics: Aged; Aged, 80 and over; Antigens, CD; Female; Flow Cytometry; Humans; Immunophenotyping; Lymphocytes; Male; Middle Aged; Prospective Studies; Sezary Syndrome; Skin Neoplasms
PubMed: 34314480
DOI: 10.1182/blood.2021012286 -
Cells Nov 2022The loss of CD47 on aging cells serves as a signal to macrophages to eliminate the target. Therefore, CD47 is a "do-not-eat-me" sign preventing macrophagal phagocytosis... (Review)
Review
The loss of CD47 on aging cells serves as a signal to macrophages to eliminate the target. Therefore, CD47 is a "do-not-eat-me" sign preventing macrophagal phagocytosis via interaction with its ligand SIRPα. Malignant lymphocytes of mycosis fungoides and Sézary syndrome express CD47 highly, thus, being ideal candidates for targeted anti-CD47 therapies. The classes of current anti-CD47-SIRPα therapeutic molecules present in a large variety and include monoclonal antibodies against CD47 and SIRPα, bioengineered SIRPα proteins, miRNAs, and bispecific antibodies. We provided a detailed analysis of all available investigational drugs in a contest of cutaneous T-cell lymphoma. A combination of blockade of the CD47-SIRPα axis and secondary targets in the tumor microenvironment (TME) may improve the clinical efficacy of current immunotherapeutic approaches. We evaluated the possible combination and outlined the most promising one.
Topics: Humans; Phagocytosis; Lymphoma, T-Cell, Cutaneous; Macrophages; Antibodies, Bispecific; Skin Neoplasms; Tumor Microenvironment; CD47 Antigen
PubMed: 36429020
DOI: 10.3390/cells11223591 -
The Oncologist Aug 2023Mogamulizumab is being increasingly prescribed for the treatment of T-cell lymphomas (MF/SS/ATLL). We conducted a retrospective cohort study to identify muscular...
Mogamulizumab is being increasingly prescribed for the treatment of T-cell lymphomas (MF/SS/ATLL). We conducted a retrospective cohort study to identify muscular immune-related adverse events (irAEs) associated with mogamulizumab in patients with T-cell lymphoma followed at Dana-Farber Cancer Institute from January 2015 to June 2022. We identified 5 cases of mogamulizumab-associated myositis and/or myocarditis (MAM/Mc), 2 additionally affected by myasthenia gravis, among 42 patients with T-cell lymphoma. Three cases experienced -mogamulizumab-associated rash (MAR) prior to developing MAM/Mc. The incidence (n = 5/42, 11.9%) of muscular mogamulizumab-associated irAEs may be higher than has been previously reported in clinical trials and may be of late onset (a median of 5 cycles and as late as 100 days from the last infusion). We highlight the utility of IVIG, together with systemic corticosteroids, for the treatment of these potentially fatal side effects associated with mogamulizumab therapy.
Topics: Humans; Myocarditis; Retrospective Studies; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Myositis; Myasthenia Gravis
PubMed: 37285523
DOI: 10.1093/oncolo/oyad155